Soluble amyloid-beta oligomer (AβO) (AβO)

Soluble amyloid-beta oligomers (AβOs) are small, diffusible aggregates of the amyloid-beta peptide that play a central role in the pathogenesis of Alzheimer's disease. Unlike the insoluble fibrils found in amyloid plaques, these soluble species are highly neurotoxic and are considered the primary drivers of synaptic dysfunction and cognitive decline [1, 11, 16]. AβOs exert their toxic effects by binding to neuronal receptors, disrupting long-term potentiation (LTP), and inducing long-term depression (LTD), which impairs memory formation [5, 12, 22]. They also trigger downstream pathological cascades, including the hyperphosphorylation of tau protein and the formation of neurofibrillary tangles [4, 18]. Therapeutic interventions targeting AβOs include monoclonal antibodies designed to neutralize or clear these toxic species, as well as small molecules that inhibit their assembly [9, 10, 17]. Clinical evidence from drugs like lecanemab suggests that selectively targeting soluble aggregated forms of amyloid-beta can slow the progression of cognitive impairment in early-stage Alzheimer's patients [4, 22]. However, these therapies are often associated with safety concerns such as amyloid-related imaging abnormalities (ARIA), characterized by brain edema or microhemorrhages [15, 19, 20].

Other names

Amyloid-beta-derived diffusible ligands (ADDLs)Aβ oligomersSoluble Aβ aggregatesAmyloid-beta protofibrilssAβO

Monoclonal antibody-mediated neutralization and clearance of toxic aggregates, and inhibition of oligomer assembly.